PROJECT SUMMARY Vaxiion proposes to evaluate the potential for bacterial minicells as an immunomodulatory therapy for use in intermediate and high-risk non-muscle invasive bladder cancer (NMIBC). The proposed product would be formulated and labeled for intravesical administration and be comprised of bacterial minicells, engineered to have enhanced anti-tumor and immunomodulatory properties. Vaxiion has preliminarily demonstrated that minicells can be engineered to have enhanced anti-tumor activity when administered intravenously in several different pre-clinical models of human cancer and now seeks to explore the possibility of using minicells as an immunomodulatory therapy for use in intermediate and high-risk NMIBC patients where the current standard of care is cytoscopic transuretheral resection of bladder tumor (TURBT) followed 14 days later by the intravesical administration of a live bacterium, Bacillus Calmette-Guerin (BCG). Because the recommended treatment guideline for NMIBC patients that are BCG-refractory, BCG-resistant, or BCG-relapsed (together 45-50%) and for those patients that are BCG-intolerant (~20%) is immediate cystectomy and urinary diversion, which exacts a heavy toll in the form of acute and chronic morbidity, we feel major opportunity in this patient population exist. Vaxiion's minicells are well suited for the job because they lack bacterial chromosomes and are non-living, and therefore may provide the immunomodulatory benefits of BCG without viability-associated toxicity. Reducing toxicity while maintaining immunomodulatory benefit would be a useful characteristic of a product used to treat BCG failure and BCG intolerant patients who face cystectomy. Additionally, minicells, in stark contrast to live BCG, may have the potential to be given immediately post-TURBT. Administration of adjuvant therapy at this time is known to produce better outcomes using chemotherapeutics in low-risk NMIBC patients but because they provide less benefit in intermediate-risk patients and no benefit in high-risk patients when compared to BCG, chemotherapeutics are not often used. It may be ideal to start BCG therapy immediately post-TURBT in intermediate and high-risk patients, but, unfortunately, the risk of TURBT-related bladder perforation(s) leading to fatal systemic BCG infection is prohibitive. Vaxiion intends to test the feasibility of this approach using a highly specialized set of models developed at Tulane University in the laboratory of Dr. W.T. Godbey, and when successful, begin pre-clinical development of a minicell product for use in NMIBC.